DESCRIPTION: (Adapted from applicant's description) The long-term objective of the proposed studies is to gain an understanding of the role that the ph-20 gene may play in the segregation and sex ratio distortions in mice heterozygous for the Rb(6.16) or Rb(6.15) translocation. Genetic and molecular approaches will be used to support the candidacy of the gene for the dysfunction in sperm bearing these translocations, particularly those with the X-chromosome. Specifically, the following hypotheses will be tested: 1. Based on chromosome homology in the human and mouse, the murine ph-20 gene maps to the proximal region of chromosome 6 near the translocation junction and is a positional candidate for the dysfunction seen in sperm bearing the Rb(6.16) or Rb(6.15) translocation. II. The level of expression of ph-20 mRNA and its encoded protein which performs at least one essential step in fertilization is altered in males homozygous for the Rb(6.16) or Rb(6.15) compared to chromosomally normal consomic mice, and expression is haploid specific occurring at the late spermatid stage. III. The segregation and sex ratio distortion, in favor of XY zygotes, in Rb(6.16) or Rb(6.15) carriers with the C57BL/6J Y-chromosome might be altered when the translocation segregates with: a) a Y associated with a larger and rounder sperm head, and b) a deleted Y associated with head anomalies and a sex ratio distortion in favor of females. IV. Strain differences in sperm head shape, and sperm age may influence the localization of the ph-20 protein. V. The product of a spermatid-specific transcript(s) encoded by a gene(s) on the Y chromosome may interact with the ph-20 protein. The work has enormous implications for our understanding of factors affecting mammalian fertilization, and particularly for humans where segregation distortion is known to exist for Rb(13;14) and for cystic fibrosis. It could also define the genetic causes underlying certain classes of male infertility or subfertility, resulting from anomalies in sperm-egg interactions, for which screening could be done.